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A. Characteristics navigator

  1. Inheritance
    1. Hereditary (~35%) - bilateral and multicentric tumors; 10% with family history
    2. Sporadic (~65%) - unilateral, solitary tumors
  2. Chromosome 13q (Rb gene) anomaly - this is a tumor suppressor gene (see below)
  3. Frequency ~1:20,000 live births - most common intraocular malignancy of childhood
  4. Mean age of diagnosis 12-18 months - 90% of cases diagnosed before age 3

B. Geneticsnavigator

  1. Rb gene (chromosome 13q) codes for a 105kd phosphoprotein
    1. Gene is differentially phosphorylated in cell cycle
    2. Acts as a tumor suppressor gene
    3. Appears particularly important in retinal and bone growth
    4. Note that human papilloma virus (HPV) E7 protein binds to and inactivates pp105-Rb
  2. Inherited dysfunction of single Rb allele
    1. Relatively high likelihood of second allele inactivation in several cells around same time
    2. This apparently leads to poorly controlled cell growth
    3. Tumors arise in multiple foci within retina
    4. ~10% of carriers of germ-line mutations do not develop retinoblastoma
    5. All patients are at risk for osteosarcomas and second cancers
    6. Bone and soft tissue sarcoma risk increased after radiation therapy [2]
  3. Sporadic
    1. Double Rb inactivation in the same cell
    2. Very unusual event leading to unilateral disease
    3. No increased risk of secondary tumors

C. Symptoms and Signs [3]navigator

  1. Leukocoria (white appearing pupil) >60%
  2. Strabismus ~25%
  3. Decreased vision but often cannot test adequately in pediatric population
  4. Dilated fixed pupil in ~15%

D. Ophthalmoscopynavigator

  1. White mass filling globe, leukocoria
  2. Exophytic - subretinal mass causing retinal detachment
  3. Endophytic - intravitreal, mass on retinal surface obscuring vessels
  4. May have vitreous seeds or cells in anterior chamber forming "pseudohypopia"
  5. Pseudo-vonHippel vasculature

E. Procedures for Diagnosisnavigator

  1. Exam under anestheisa
  2. Ultrasound / CT - show tumor calcification
  3. Anterior chamber paracentesis

F. Differential Diagnosisnavigator

  1. Coats Disease
  2. Toxocariasis
  3. Retinopathy of prematurity
  4. Persistent hyperplastic primary vitreous
  5. Cataract
  6. Astrocytic Hamartoma

G. Therapy navigator

  1. Enucleation for primary eye with vision loss
  2. External Beam irradiation - second eye with less advanced cases
  3. Radioactive plaques
  4. Cryotherapy - small to medium tumors anterior to equator
  5. Photocoagulation - small tumor posterior to equation
  6. Chemotherapy - various combinations of agents have been used

H. Metastasesnavigator

  1. Includes skull and distal bones
  2. Spinal cord, lymph nodes, abdomen
  3. Evaluation at time of evaluation under anesthesia includes:
    1. Bone Marrow Aspiration
    2. Lumbar Puncture

References navigator

  1. Cavenee WK, Murphree AL, Shull MM, et al. 1986. NEJM. 314(19):1201 abstract
  2. Wong FL, Boice JD Jr, Abramson DH, et al. 1997. JAMA. 278(15):1262 abstract
  3. Simon JW and Kaw P. 2001. Am Fam Phys. 64(4):623 abstract